Methylphenidate available in the market to treat Attention Deficient Hyperactivity Disorder (ADHD) is dl-threo mixture. It is a controlled substance. Methylphenidate contains two chiral carbon atoms and so exists in four enantiomeric forms. Of all the forms, the studies of its threo-diastereomer revealed that d-threo isomer has been found to be more active and also showed significant metabolic difference than l-threo enantiomer.
To date, there have been several methods disclosed in the literature for preparing d-threo enantiomer of methylphenidate. For example, the process reported first by Patrick et. al. [The Journal of Pharmacology and Experimental Therapeutics, 241, 152-158 (1987)], describes the use of expensive resolving agent, 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate in the resolution of dl-threo-methylphenidate. More efficient resolutions, using a O,O-Diaroyltartaric acid or menthoxy-acetic acid or dibenzoyl-D-tartaric acid are disclosed in WO9727176, GB97/00643, U.S. Pat. No. 6,100,401, U.S. Pat. No. 6,121,453, U.S. Pat. No. 6,162,919 and U.S. Pat. No. 6,242,464. Resolution of threo-methylphenidate may also be achieved by enzymatic hydrolysis methods proposed by Prashad (1998) [U.S. Pat. No. 7,247,730] and in WO98/25902.
U.S. Pat. No. 2,957,880 discloses the resolution of erythro-phenylpiperidyl acetamide using tartaric acid. This, however, must be followed by amide hydrolysis and equilibration at the benzylic centre, to give the threo isomer of the ritalinic acid.
In addition, U.S.2002/0019535 describes the manufacture of threo-ritalinic acid by resolution of threo-ritalinic acid hydrochloride using chiral base (S)-(−)-1-phenethylamine affording the product in 77% ee.
It would be desirable to find    1) a satisfactory substrate for resolution that did not involve handling of the active drug and    2) a more practical and efficient process to produce compound with high optical purity. Ritalinic acid in threo form might be a target. threo-Ritalinic acid contains a carboxylic group and a tertiary amino function in the moiety, due to which either chiral carboxylic acid or chiral organic base can be used for resolution. The d-threo-enantiomer of ritalinic acid thus obtained can be converted to d-threo-methylphenidate hydrochloride by reaction with methanol and hydrochloric acid.
The present invention provides an improved process for preparing d- and l-threo isomers of ritalinic acid of formula I & II,
and its salt by resolution of dl-threo-ritalinic acid of the formula III using chiral carboxylic acid of the formula IV as the resolving agent.

The method of the present invention is quite preferable and economical for the preparation of d-threo-ritalinic acid as an industrial procedure and gives d-threo-ritalinic acid hydrochloride with high optical purity.
More particularly, the process involves the resolution of di-threo-ritalinic acid with (+)-dibenzoyl-D-tartaric acid to yield the desired tartrate salt of d-threo-isomer of ritalinic acid in the first step and the breaking of salt in the second step to obtain the hydrochloride form of the d-threo-isomer with high optical purity, while the l-threo-isomer and the dibenzoyltartaric acid are recovered from the mother liquors as shown below:
